One-Pot Fabrication of Hollow Porphyrinic MOF Nanoparticles with Ultrahigh Drug Loading toward Controlled Delivery and Synergistic Cancer Therapy

Hollow nanostructures have attracted significant research interest in drug delivery systems due to their high capacities for drug loading and unique physicochemical properties, showing great potential in specific biomedical applications. Herein, hollow porphyrinic metal–organic framework (H-PMOF) nanoparticles with a mesoporous spherical shell have been fabricated via a facile self-sacrificial ZIF-8 nanoparticle template strategy. The H-PMOF nanoplatform not only demonstrates a greatly enhanced photodynamic therapy efficacy compared with nonhollow porphyrinic MOF nanoparticles but also can be used as a superior drug carrier to co-load doxorubicin (DOX) and indocyanine green (ICG) with an ultrahigh drug-loading capacity of 635%. Furthermore, cancer cell membrane camouflage of the (DOX and ICG)@H-PMOF composite nanoparticles affords a biomimetic nanoplatform, that is, (DOX and ICG)@H-PMOF@mem (DIHPm for short), with an outstanding homologous tumor-targeting and immune-escaping ability. Interestingly, DIHPm shows both pH-controlled and near-infrared laser-triggered DOX release. Both in vitro and in vivo studies of DIHPm demonstrate an excellent imaging-guided synergistic photodynamic/photothermal/chemotherapy anticancer activity with negligible systemic toxicity. The development of the high-performance H-PMOF nanoplatform provides new insights into the design of MOF-based multifunctional nanomedicines for combination cancer therapy and precise theranostics.